PFKA_GEOSE
ID PFKA_GEOSE Reviewed; 319 AA.
AC P00512;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=ATP-dependent 6-phosphofructokinase {ECO:0000255|HAMAP-Rule:MF_00339};
DE Short=ATP-PFK {ECO:0000255|HAMAP-Rule:MF_00339};
DE Short=Phosphofructokinase {ECO:0000255|HAMAP-Rule:MF_00339};
DE EC=2.7.1.11 {ECO:0000255|HAMAP-Rule:MF_00339};
DE AltName: Full=Phosphohexokinase {ECO:0000255|HAMAP-Rule:MF_00339};
GN Name=pfkA {ECO:0000255|HAMAP-Rule:MF_00339}; Synonyms=pfk;
OS Geobacillus stearothermophilus (Bacillus stearothermophilus).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Geobacillus.
OX NCBI_TaxID=1422;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2956156; DOI=10.1016/0378-1119(87)90348-9;
RA French B.A., Chang S.H.;
RT "Nucleotide sequence of the phosphofructokinase gene from Bacillus
RT stearothermophilus and comparison with the homologous Escherichia coli
RT gene.";
RL Gene 54:65-71(1987).
RN [2]
RP PROTEIN SEQUENCE.
RX PubMed=6447595; DOI=10.1111/j.1432-1033.1980.tb04754.x;
RA Kolb E., Hudson P.J., Harris J.I.;
RT "Phosphofructokinase: complete amino-acid sequence of the enzyme from
RT Bacillus stearothermophilus.";
RL Eur. J. Biochem. 108:587-597(1980).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 300-319.
RX PubMed=8436141; DOI=10.1111/j.1432-1033.1993.tb17618.x;
RA Sakai H., Ohta T.;
RT "Molecular cloning and nucleotide sequence of the gene for pyruvate kinase
RT of Bacillus stearothermophilus and the production of the enzyme in
RT Escherichia coli. Evidence that the genes for phosphofructokinase and
RT pyruvate kinase constitute an operon.";
RL Eur. J. Biochem. 211:851-859(1993).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=8136379; DOI=10.1021/bi00177a036;
RA Byrnes M., Zhu X., Younathan E.S., Chang S.H.;
RT "Kinetic characteristics of phosphofructokinase from Bacillus
RT stearothermophilus: MgATP nonallosterically inhibits the enzyme.";
RL Biochemistry 33:3424-3431(1994).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=156307; DOI=10.1038/279500a0;
RA Evans P.R., Hudson P.J.;
RT "Structure and control of phosphofructokinase from Bacillus
RT stearothermophilus.";
RL Nature 279:500-504(1979).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH MAGNESIUM; ADP AND
RP FRUCTOSE-6-PHOSPHATE.
RX PubMed=6115424; DOI=10.1098/rstb.1981.0059;
RA Evans P.R., Farrants G.W., Hudson P.J.;
RT "Phosphofructokinase: structure and control.";
RL Philos. Trans. R. Soc. Lond., B, Biol. Sci. 293:53-62(1981).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH ALLOSTERIC INHIBITOR.
RX PubMed=2136935; DOI=10.1038/343140a0;
RA Schirmer T., Evans P.R.;
RT "Structural basis of the allosteric behaviour of phosphofructokinase.";
RL Nature 343:140-145(1990).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) IN COMPLEX WITH FRUCTOSE-6-PHOSPHATE.
RX PubMed=12390023; DOI=10.1021/bi0263412;
RA Riley-Lovingshimer M.R., Ronning D.R., Sacchettini J.C., Reinhart G.D.;
RT "Reversible ligand-induced dissociation of a tryptophan-shift mutant of
RT phosphofructokinase from Bacillus stearothermophilus.";
RL Biochemistry 41:12967-12974(2002).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS).
RX PubMed=22212099; DOI=10.1021/bi201548p;
RA Mosser R., Reddy M.C., Bruning J.B., Sacchettini J.C., Reinhart G.D.;
RT "Structure of the apo form of Bacillus stearothermophilus
RT phosphofructokinase.";
RL Biochemistry 51:769-775(2012).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH PHOSPHOENOLPYRUVIC
RP ACID.
RX PubMed=23859543; DOI=10.1021/bi4002503;
RA Mosser R., Reddy M.C., Bruning J.B., Sacchettini J.C., Reinhart G.D.;
RT "Redefining the role of the quaternary shift in Bacillus stearothermophilus
RT phosphofructokinase.";
RL Biochemistry 52:5421-5429(2013).
CC -!- FUNCTION: Catalyzes the phosphorylation of D-fructose 6-phosphate to
CC fructose 1,6-bisphosphate by ATP, the first committing step of
CC glycolysis. {ECO:0000255|HAMAP-Rule:MF_00339,
CC ECO:0000269|PubMed:8136379}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 1,6-
CC bisphosphate + H(+); Xref=Rhea:RHEA:16109, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:32966, ChEBI:CHEBI:57634,
CC ChEBI:CHEBI:456216; EC=2.7.1.11; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_00339, ECO:0000269|PubMed:8136379};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00339,
CC ECO:0000269|PubMed:6115424};
CC -!- ACTIVITY REGULATION: Allosterically activated by ADP and other
CC diphosphonucleosides, and allosterically inhibited by
CC phosphoenolpyruvate. {ECO:0000255|HAMAP-Rule:MF_00339,
CC ECO:0000269|PubMed:2136935, ECO:0000269|PubMed:23859543,
CC ECO:0000305|PubMed:8136379}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.07 mM for ATP {ECO:0000269|PubMed:8136379};
CC KM=0.033 mM for fructose 6-phosphate {ECO:0000269|PubMed:8136379};
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 3/4.
CC {ECO:0000255|HAMAP-Rule:MF_00339}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_00339,
CC ECO:0000269|PubMed:12390023, ECO:0000269|PubMed:2136935,
CC ECO:0000269|PubMed:23859543, ECO:0000269|PubMed:6115424}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00339}.
CC -!- MISCELLANEOUS: In the R state the 6-P group of fructose 6-phosphate
CC (F6P) is bound by His-249 from one chain and Arg-162 and Arg-243 from
CC an adjacent chain. In the T state a conformation change moves Arg-162
CC away from the substrate. Glu-161 takes its place, hence repelling the
CC phosphate of ATP. {ECO:0000305|PubMed:2136935}.
CC -!- SIMILARITY: Belongs to the phosphofructokinase type A (PFKA) family.
CC ATP-dependent PFK group I subfamily. Prokaryotic clade 'B1' sub-
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_00339}.
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DR EMBL; M15643; AAA22656.1; -; Genomic_DNA.
DR EMBL; D13095; BAA02405.1; -; Genomic_DNA.
DR PIR; A27474; KIBSFF.
DR RefSeq; WP_033014452.1; NZ_RCTK01000004.1.
DR PDB; 1MTO; X-ray; 3.20 A; A/B/C/D/E/F/G/H=1-319.
DR PDB; 3PFK; X-ray; 2.40 A; A=1-319.
DR PDB; 3U39; X-ray; 2.79 A; A/B/C/D=1-319.
DR PDB; 4I36; X-ray; 2.30 A; A/B/C/D=1-319.
DR PDB; 4I4I; X-ray; 2.49 A; A/B/C/D=1-319.
DR PDB; 4I7E; X-ray; 2.00 A; A/B/C/D=1-319.
DR PDB; 4PFK; X-ray; 2.40 A; A=1-319.
DR PDB; 6PFK; X-ray; 2.60 A; A/B/C/D=1-319.
DR PDBsum; 1MTO; -.
DR PDBsum; 3PFK; -.
DR PDBsum; 3U39; -.
DR PDBsum; 4I36; -.
DR PDBsum; 4I4I; -.
DR PDBsum; 4I7E; -.
DR PDBsum; 4PFK; -.
DR PDBsum; 6PFK; -.
DR AlphaFoldDB; P00512; -.
DR SMR; P00512; -.
DR DrugBank; DB02726; 2-Phosphoglycolic Acid.
DR DrugBank; DB04493; Fructose-6-phosphate.
DR DrugBank; DB09344; Invert sugar.
DR GeneID; 58572630; -.
DR BRENDA; 2.7.1.11; 623.
DR SABIO-RK; P00512; -.
DR UniPathway; UPA00109; UER00182.
DR EvolutionaryTrace; P00512; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003872; F:6-phosphofructokinase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IEA:InterPro.
DR CDD; cd00763; Bacterial_PFK; 1.
DR Gene3D; 3.40.50.460; -; 1.
DR HAMAP; MF_00339; Phosphofructokinase_I_B1; 1.
DR InterPro; IPR022953; ATP_PFK.
DR InterPro; IPR012003; ATP_PFK_prok-type.
DR InterPro; IPR012828; PFKA_ATP_prok.
DR InterPro; IPR015912; Phosphofructokinase_CS.
DR InterPro; IPR000023; Phosphofructokinase_dom.
DR InterPro; IPR035966; PKF_sf.
DR Pfam; PF00365; PFK; 1.
DR PIRSF; PIRSF000532; ATP_PFK_prok; 1.
DR PRINTS; PR00476; PHFRCTKINASE.
DR SUPFAM; SSF53784; SSF53784; 1.
DR TIGRFAMs; TIGR02482; PFKA_ATP; 1.
DR PROSITE; PS00433; PHOSPHOFRUCTOKINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; ATP-binding; Cytoplasm;
KW Direct protein sequencing; Glycolysis; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Transferase.
FT CHAIN 1..319
FT /note="ATP-dependent 6-phosphofructokinase"
FT /id="PRO_0000111935"
FT ACT_SITE 127
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339"
FT BINDING 11
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339"
FT BINDING 21..25
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339,
FT ECO:0000269|PubMed:6115424"
FT BINDING 59
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339,
FT ECO:0000269|PubMed:6115424"
FT BINDING 72..73
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339,
FT ECO:0000269|PubMed:6115424"
FT BINDING 102..105
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339"
FT BINDING 103
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339,
FT ECO:0000269|PubMed:6115424"
FT BINDING 125..127
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339,
FT ECO:0000269|PubMed:12390023, ECO:0000269|PubMed:6115424"
FT BINDING 154
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339,
FT ECO:0000269|PubMed:6115424"
FT BINDING 162
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339,
FT ECO:0000269|PubMed:6115424"
FT BINDING 169..171
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339,
FT ECO:0000269|PubMed:12390023, ECO:0000269|PubMed:6115424"
FT BINDING 185..187
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339,
FT ECO:0000269|PubMed:6115424"
FT BINDING 211
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339,
FT ECO:0000269|PubMed:6115424"
FT BINDING 213..215
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339,
FT ECO:0000269|PubMed:6115424"
FT BINDING 222
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339,
FT ECO:0000269|PubMed:12390023, ECO:0000269|PubMed:6115424"
FT BINDING 243
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339,
FT ECO:0000269|PubMed:12390023, ECO:0000269|PubMed:6115424"
FT BINDING 249..252
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00339,
FT ECO:0000269|PubMed:12390023, ECO:0000269|PubMed:6115424"
FT CONFLICT 12
FT /note="D -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 35..37
FT /note="Missing (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 43
FT /note="G -> V (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 82
FT /note="Q -> E (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 95
FT /note="E -> Q (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="G -> L (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 3..11
FT /evidence="ECO:0007829|PDB:4I7E"
FT HELIX 16..29
FT /evidence="ECO:0007829|PDB:4I7E"
FT STRAND 33..37
FT /evidence="ECO:0007829|PDB:4I7E"
FT HELIX 40..46
FT /evidence="ECO:0007829|PDB:4I7E"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:4I7E"
FT HELIX 54..57
FT /evidence="ECO:0007829|PDB:4I7E"
FT HELIX 74..77
FT /evidence="ECO:0007829|PDB:4I7E"
FT HELIX 81..91
FT /evidence="ECO:0007829|PDB:4I7E"
FT STRAND 97..102
FT /evidence="ECO:0007829|PDB:4I7E"
FT HELIX 103..114
FT /evidence="ECO:0007829|PDB:4I7E"
FT STRAND 119..127
FT /evidence="ECO:0007829|PDB:4I7E"
FT HELIX 139..153
FT /evidence="ECO:0007829|PDB:4I7E"
FT STRAND 159..168
FT /evidence="ECO:0007829|PDB:4I7E"
FT HELIX 175..183
FT /evidence="ECO:0007829|PDB:4I7E"
FT STRAND 187..190
FT /evidence="ECO:0007829|PDB:4I7E"
FT HELIX 198..210
FT /evidence="ECO:0007829|PDB:4I7E"
FT STRAND 216..221
FT /evidence="ECO:0007829|PDB:4I7E"
FT TURN 222..224
FT /evidence="ECO:0007829|PDB:4I7E"
FT HELIX 227..238
FT /evidence="ECO:0007829|PDB:4I7E"
FT STRAND 241..246
FT /evidence="ECO:0007829|PDB:4I7E"
FT HELIX 248..252
FT /evidence="ECO:0007829|PDB:4I7E"
FT HELIX 258..277
FT /evidence="ECO:0007829|PDB:4I7E"
FT STRAND 281..287
FT /evidence="ECO:0007829|PDB:4I7E"
FT STRAND 290..295
FT /evidence="ECO:0007829|PDB:4I7E"
FT HELIX 296..300
FT /evidence="ECO:0007829|PDB:4I7E"
FT HELIX 308..317
FT /evidence="ECO:0007829|PDB:4I7E"
SQ SEQUENCE 319 AA; 34119 MW; EE968D39BA30712B CRC64;
MKRIGVLTSG GDSPGMNAAI RSVVRKAIYH GVEVYGVYHG YAGLIAGNIK KLEVGDVGDI
IHRGGTILYT ARCPEFKTEE GQKKGIEQLK KHGIEGLVVI GGDGSYQGAK KLTEHGFPCV
GVPGTIDNDI PGTDFTIGFD TALNTVIDAI DKIRDTATSH ERTYVIEVMG RHAGDIALWS
GLAGGAETIL IPEADYDMND VIARLKRGHE RGKKHSIIIV AEGVGSGVDF GRQIQEATGF
ETRVTVLGHV QRGGSPTAFD RVLASRLGAR AVELLLEGKG GRCVGIQNNQ LVDHDIAEAL
ANKHTIDQRM YALSKELSI
